[Individualization of the amikacin administration regimen on the basis of the relationship between its pharmacokinetics and the patient's status].
Dosage individualization based on quantitative relationships between pharmacokinetic parameters and anatomophysiological and/or pathological factors, patient's factors (PFs) is of importance in designing optimal regimens. Unfortunately, the attempts to correlate aminoglycoside pharmacokinetic parameters and PFs often failed perhaps due to insufficient numbers of PFs under investigation. That is why we sought to involve more PFs, especially nontraditional ones, for explaining intersubject variability of the amikacin model-independent parameter in 20 patients with purulent inflammatory processes. Amikacin plasma concentrations in specimens collected 0.5, 1, 2, 4, 5 and 6 hours after the drug administration (500 mg, i.v.) were determined with the FRIA-technique (TDx, Abbott). The mean values of the total clearance (Cl), steady-state volume of distribution (Vss) and the mean residence time (MRT) were 87.5 +/- 18.4 ml/(h.kg), 0.33 +/- 0.07 l/kg and 4.0 +/- 0.6 h, respectively. Stepwise multivariate regression analysis made it possible to establish statistically significant correlations between the Cl and 8 PFs, including age, sodium plasma concentrations, plasma osmolarity, partial pressure of oxygen and carbon dioxide, volumes of transfused plasma and blood and artificial pulmonary ventilation (r = 0.99), as well as between the MRT and 6 PFs, including sex, plasma osmolarity, plasma creatinine concentrations, volumes of transfused plasma and artificial pulmonary ventilation (r = 0.94). Multiple correlations were also found between the area under the drug concentration/time curve and 11 PFs (r = 0.99). The coefficient of the multiple correlation between the Vss and volume of the transfused plasma proved to be much lower (r = 0.67). The multiple regression equation for the Cl prediction provided a reliable indirect estimation of the parameter individual values without the amikacin concentration data. Thus, it appeared possible to adjust the aminoglycoside dosage by taking into account 8 PFs before the TDM data were available.
Firsov
A A
AA
All-Union Research Institute of Antibiotics, Moscow.
Nasonov
V N
VN
Murav'eva
S A
SA
Portnoĭ
Iu A
IuA
Savitskaia
K I
KI
D000328:Adult; D000368:Aged; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012129:Respiratory Function Tests; D014882:Water-Electrolyte Balance / Q000502:physiology
D000583:Amikacin
Individualizatsiia skhem vvedeniia amikatsina na osnove vzaimosviazeĭ ego farmakokinetiki i sostoianiia bol'nogo.